• Shock · Jul 2009

    The role of endogenous and exogenous ligands for the peroxisome proliferator-activated receptor alpha (PPAR-alpha) in the regulation of inflammation in macrophages.

    • Concetta Crisafulli and Salvatore Cuzzocrea.
    • Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina Torre Biologica, Policlinico Universitario, Messina, Italy.
    • Shock. 2009 Jul 1; 32 (1): 62-73.

    AbstractThe aim of the present study was to evaluate the role of endogenous and exogenous peroxisome proliferator-activated receptor alpha (PPAR-alpha), a nuclear receptor, on the regulation of inflammation in macrophages. To address this question, we have stimulated peritoneal macrophages from PPAR-alpha wild-type mice and PPAR-alpha knockout mice (PPAR-alpha) with 10 microg/mL LPS and 100 U/mL IFN-gamma. We report here that the absence of a functional PPAR-alpha gene in PPAR-alpha knockout mice resulted in a significant augmentation of various inflammatory parameters in peritoneal macrophages. In particular, we have clearly demonstrated that PPAR-alpha gene deletion increases (1) the mitogen-activated protein kinase phosphorylation (extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38), (2) nuclear factor-kappaB activation, (3) IkappaB-alpha degradation, (4) iNOS expression and NO formation, and (5) cyclooxygenase 2 expression and prostaglandin E2 formation caused by LPS/IFN-gamma stimulation. On the contrary, the incubation of peritoneal macrophages from PPAR-alpha wild type with clofibrate (2 mM) at 2 h before the LPS and IFN-gamma stimulation significantly reduced the expression and the release of the proinflammatory mediators. To elucidate whether the protective effects of clofibrate is related to activation of the PPAR-alpha receptor, we also investigated the effect of clofibrate treatment on PPAR-alpha-deficient mice. The absence of the PPAR-alpha receptor significantly abolished the protective effect of the PPAR-alpha agonist against LPS/IFN-gamma-induced macrophage inflammation. In conclusion, our study demonstrates that the endogenous and exogenous PPAR-alpha ligands reduce the degree of macrophage inflammation caused by LPS/IFN-gamma stimulation.

      Pubmed     Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…